Molecular methods are such an integrated part of insect systematics that we tend to forget that the methods have only been around for a few decades. Despite morphology being as important today as it was 100 years ago (e.g. see Systematic Entomology, Virtual Issue December 2010), it may be as hard for today’s graduate students working on insect systematics to imagine a world without molecular data as it would be for today’s children to imagine a world without DVDs and iPhones. Nevertheless, only a decade ago insect molecular phylogenetics and systematics was very much in its infancy and still viewed by many to be controversial and often misleading. Since then molecular insect systematics has undergone immense changes: from studies limited to a few (often mitochondrial) gene fragments and few taxa; to large-scale phylogenomic studies, studies combining multiple genes with large morphological and ecological datasets, and population studies focused on phylogeography or species delimitation based on e.g. SNIPS and micro satellites. Studies focused on Lepidoptera have played a highly important role in this development, in part due to the general focus on Lepidoptera (and in particular butterflies) as model organisms for both evolutionary studies and conservation, but also and importantly because collaborations with a large, skilled and enthusiastic international community of amateur collectors have made access to material suitable for molecular studies easier than in many other groups. This virtual issue celebrates the advances in Lepidoptera molecular systematics in the 21st century from the early, humble beginning to today’s genomic-scale studies by directing our readers to 26 papers on various aspects of Lepidoptera molecular systematics published in Systematic Entomology since 2000.